Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

Immunity to hepatitis B vaccine in Tanzanian under-5 children.

BACKGROUND: Hepatitis B vaccine was introduced in Tanzania in 2002 and is administered as DPT-hepatitis B at 4, 8 and 12 weeks of life. AIM: To determine immunity to hepatitis B virus in children under 5 years attending reproductive and child health (RCH) clinics. METHODS: A cross-sectional, health facility-based study was conducted between July and December 2007 at Temeke, Amana and Mwananyamala municipal hospitals in Dar es Salaam, Tanzania. Children under 5 years who had received DPT-HB vaccine as evidenced by RCH card number 1 were included. Blood samples were collected to determine hepatitis B surface antigen (HB(s)Ag) and antibodies to hepatitis B surface antigen (anti-HB(s)) and hepatitis B core antigen (Anti-HB(c)). An anti-HB(s) level of > or =10 mIU/ml is regarded as protective. Nutritional and HIV status were also determined. RESULTS: A total of 296 children under 5 years vaccinated with DPT-HB were recruited, 153 (51.7%) of whom were male. Altogether, 205 (69.3%) children had anti-HB(s) levels > or =10 mIU/ml. The number of DPT-HB vaccine doses, time interval since last DPT-HB dose and HIV status were significant predictors of anti-HB(s) levels. Five children (1.7%) were positive for HB(s)Ag, suggesting possible vertical transmission. No child had anti-HB(c) antibodies. CONCLUSION: More than two-thirds of children under 5 years had protective anti-HB(s) levels. A change in the hepatitis B immunisation schedule to include a dose immediately after birth should improve immunity.

Enhancing adherence to antiretroviral therapy at the HIV clinic in resource constrained countries; the Tanzanian experience.

OBJECTIVE: To evaluate various strategies aimed at improving adherence to antiretroviral therapy (ART). METHODS: Patients initiated on ART at Muhimbili National Hospital HIV clinic were randomly assigned to either regular adherence counseling, regular counseling plus a calendar, or regular counseling and a treatment assistant. Patients were seen monthly; during these meetings self-reported adherence to treatment was recorded. Disease progression was monitored clinically and immunologically. RESULTS: Of the 621 patients randomized, 312 received regular counseling only, 242 regular counseling and calendars, while 67 had treatment assistants in addition to regular counseling. The mean (SD) follow-up time was 14.5 (4.6) months. During follow-up 20 (3.2%) patients died, and 102 (16.4%) were lost to follow-up; this was similar in all groups. In 94.8% of all visits, patients reported to have adhered to treatment. In only 39 (0.7%) visits did patients report a < or = 95% adherence. There were no differences in adherence (P = 0.573) or differences in CD4 count and weight changes over time in the interventions. CONCLUSIONS: Good adherence to ART is possible in resource constrained countries. Persistent adherence counseling in clinic settings by itself may be effective in improving adherence to ART.

Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia.

SUMMARY: The aim of this study was to compare the prevalence and factors associated with genital tract infections among HIV-infected pregnant women from African sites. Participants were recruited from Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. Genital tract infections were assessed at baseline. Of 2627 eligible women enrolled, 2292 were HIV-infected. Of these, 47.8% had bacterial vaginosis (BV), 22.4% had vaginal candidiasis, 18.8% had trichomoniasis, 8.5% had genital warts, 2.6% had chlamydia infection, 2.2% had genital ulcers and 1.7% had gonorrhoea. The main factors associated with genital tract infections included genital warts (adjusted odds ratio [AOR] 1.8, 95% CI 1.2-2.7), genital ulcers (AOR 2.4, 95% CI 1.2-5.1) and abnormal vaginal discharge (AOR 2.5, 95% CI 1.9-3.3) for trichomoniasis. BV was the most common genital tract infection followed by candidiasis and trichomoniasis. Differences in burdens and risk factors call for enhanced interventions for identification of genital tract infections among HIV-infected women.

Zinc and multivitamin supplementation have contrasting effects on infant iron status: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Zinc (Zn) supplementation adversely affects iron status in animal and adult human studies, but few trials have included young infants. The objective of this study was to determine the effects of Zn and multivitamin (MV) supplementation on infant hematologic and iron status. SUBJECTS/METHODS: In a double-blind RCT, Tanzanian infants were randomized to daily, oral Zn, MV, Zn and MV or placebo treatment arms at the age of 6 weeks of life. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12 and 18 months of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 months. RESULTS: In logistic regression models, Zn treatment was associated with greater odds of ID (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.0-3.3)) and MV treatment was associated with lower odds (OR 0.49 (95% CI 0.3-0.9)). In Cox models, MV was associated with a 28% reduction in risk of severe anemia (hazard ratio (HR)=0.72 (95% CI 0.56-0.94)) and a 26% reduction in the risk of severe microcytic anemia (HR=0.74 (0.56-0.96)) through 18 months. No effects of Zn on risk of anemia were seen. Infants treated with MV alone had higher mean Hb (9.9 g/dl (95% CI 9.7-10.1)) than those given placebo (9.6 g/dl (9.4-9.8)) or Zn alone (9.6 g/dl (9.4-9.7)). CONCLUSIONS: MV treatment improved iron status in infancy, whereas Zn worsened iron status but without an associated increase in risk for anemia. Infants in long-term Zn supplementation programs at risk for ID may benefit from screening and/or the addition of a MV supplement.

Zinc supplementation to HIV-1-infected pregnant women: effects on maternal anthropometry, viral load, and early mother-to-child transmission.

OBJECTIVE: To examine the effect of zinc supplementation to HIV-1-infected pregnant women on viral load, early mother-to-child transmission of HIV (MTCT), and wasting. DESIGN: Double-blind placebo-controlled randomized clinical trial. SETTING: Antenatal clinic in Dar es Salaam, Tanzania. SUBJECTS: Four hundred HIV-1-infected pregnant women. METHODS: Women 12-27 weeks of gestation were randomly assigned to receive a daily oral dose of 25 mg zinc or placebo from the day of the first prenatal visit until 6 weeks postdelivery. Weight and mid-upper arm circumference (MUAC) were measured monthly. HIV status of the babies was assessed at birth and at 6 weeks postpartum. Viral load was assessed in a random sample of 100 women at baseline and at the end of the study. RESULTS: Zinc had no effects on maternal viral load or early MTCT. Supplementation was related to a significant threefold increase in the risk of wasting (reaching a MUAC value <22 cm) during an average 22 weeks of observation (RR=2.7, 95%CI=1.1, 6.4, P=0.03), and to a 4 mm decline in MUAC during the second trimester (P=0.02). CONCLUSIONS: Zinc supplementation to HIV-infected pregnant women offers no benefits on viral load or MTCT. The clinical relevance of an apparent decrease in MUAC associated with zinc supplementation is yet to be ascertained. These findings together with the lack of effect on fetal outcomes (reported previously) do not provide support for the addition of zinc supplements to the standard of prenatal care among HIV-infected women.

Immunity to tetanus in male adults in Dar es Salaam, Tanzania.

OBJECTIVE: To determine immunity to tetanus in male blood donors with previous diphtheria-pertussis-tetanus (DPT)/tetanus toxoid (TT) vaccination. DESIGN: A cross sectional study, conducted in September 1999. SETTING: Blood bank, Muhimbili Medical Centre, Dar es Salaam, Tanzania. METHODS: Using an antigen competition ELISA technique, serum tetanus anti-toxin levels in two hundred male blood donors were determined. RESULTS: Vaccination history was absent in 43 (21.5%) blood donors, whereas 60 (30%) and 97 (48.5%) reported childhood DPT and TT vaccination, respectively. Tetanus anti-toxin was undetectable in 47 (23.5%) blood donors and the levels were below that considered protective (> or = 0.1 IU/ml) in 25 (12.5%). Among those with undetectable level, 43 (91.5%) had no vaccination history. Time after last DPT/TT vaccination correlated significantly with tetanus anti-toxin levels (r2=-0.331, p=0.001). In multivariate analysis, TT doses received and time after last vaccination explained 4.8% and 29.4%, respectively, of the variations in tetanus anti-toxin levels. CONCLUSION: Seventy two (36%) male blood donors were susceptible to tetanus and the susceptibility was highest from 48 years. A regular TT booster dose at 10 yearly intervals is recommended to provide adequate and long lasting immunity in male adults. Proper keeping of vaccination records is emphasised.

Tetanus immunity among pregnant women attending antenatal care in Dar es Salaam, Tanzania.

This study was conducted to investigate immunity to tetanus among pregnant women with verbal histories or documentation of having been vaccinated under the current five-dose tetanus toxoid (TT) schedule. It examined sera from 176 pregnant women attending antenatal care at Muhimbili Medical Centre in Dar es Salaam, Tanzania. Tetanus antitoxin level of 0.1 IU/ml was considered protective. Our findings show that 94.9% of women had tetanus antitoxin > or = 0.1 IU/ml. Multivariate analysis revealed that time after last vaccination, TT doses received and TT vaccination status explained 7.5%, 5.7% and 2.3% of variations in tetanus antitoxin levels respectively. Pregnant women with non-protective levels of tetanus antitoxin (5.1%) pose great risks of neonatal tetanus to their newborns and are also susceptible to maternal tetanus. Proper keeping of TT vaccination records is vitally important to avoid hyper-immunisation.

Detecting virological failure in HIV-infected Tanzanian children.

BACKGROUND: The performance of clinical and immunological criteria to predict virological failure in HIV-infected children receiving antiretroviral therapy (ART) is not well documented. OBJECTIVE: To determine the validity of clinical and immunological monitoring in detecting virological failure in children on ART. METHODS: A total of 218 children were included in the study. All were from care and treatment clinics in Dar es Salaam, Tanzania. Their mean age was 10.6 years, 122 (56.0%) were males, and the mean time on ART was 40.9 months. The study was conducted from August 2011 to March 2012. Data on sociodemographic and clinical characteristics and immunological and virological failure were based on World Health Organization definitions. Blood samples were collected for CD4+ T-cell count and viral load tests. RESULTS: Of 217 children with available viral load results, 124 (57.1%) had virological failure (>400 copies/mL), 25.0% immunological failure and 11.5% clinical failure. The sensitivity, specificity, positive predictive value and negative predictive value of clinical criteria were 12.9%, 90.3%, 64.0% and 43.8%, respectively, those for immunological criteria 22.6%, 73.1%, 53.3% and 41.4%, and those for the combination of clinical and immunological monitoring 25.8%, 69.9%, 53.3% and 41.4%. Children who received nevirapine (NVP)-based regimens were two times more likely (odds ratio 2.0; 95% confidence interval 1.20 - 3.64) to have virological failure than those on efavirenz and protease inhibitor-based regimens. CONCLUSIONS: The study demonstrated poor performance of currently recommended clinical and immunological criteria for monitoring HIV-infected children on ART. Moreover, children on NVP-based regimens had a higher risk of developing virological failure than those on other regimens.

Predictors of stunting, wasting and underweight among Tanzanian children born to HIV-infected women.

BACKGROUND/OBJECTIVES: Children born to human immunodeficiency virus (HIV)-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized. The objective of this study was to identify maternal, socioeconomic and child characteristics that are associated with stunting, wasting and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks of age for 24 months. SUBJECTS/METHODS: Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant's birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting and underweight. RESULTS: A total of 2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birth weight (<2500 g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting and underweight was 8.7, 7.2 and 7.0 months, respectively. Low maternal education, few household possessions, low infant birth weight, child HIV infection and male sex were all independent predictors of stunting, wasting and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted. CONCLUSIONS: Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women.

Prevalence of genotypic resistance to antiretroviral drugs in treatment-naive youths infected with diverse HIV type 1 subtypes and recombinant forms in Dar es Salaam, Tanzania.

As human immunodeficiency virus (HIV) diversity may have an impact on both vaccine efficacy and drug resistance, it is important to have knowledge of circulating genetic variants. With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. This study aimed to determine the circulating HIV subtypes and recombinant forms, as well as the prevalence of ARV drug resistance mutations, among 75 treatment-naive HIV-infected youths in Dar es Salaam, Tanzania. Gag (n = 48), partial pol (n = 44), and partial env (n = 35) sequencing was performed; all three regions were sequenced in 26 samples. Evidence of infection with recombinant viruses was found in 12 (46%) participants; AC recombinants were the most commonly detected and they were identified in six (23%) participants. Of individuals infected with nonrecombinant strains, subtype A was most commonly detected in seven (27%) participants, followed by subtype C detected in six (23%) participants and subtype D detected in one (4%) participant. Among the pol sequences from 44 individuals, three (7%) had resistance to nucleoside reverse transcriptase (RT) inhibitors and four (9%) had nonnucleoside RT inhibitor resistance mutations. Of these, three (7%) individuals were infected with viruses with cross-resistance mutations to both classes of RT inhibitors. These resistant mutations were all associated with drugs currently used in first-line therapy and in the prevention of vertical transmission. This high prevalence of resistance mutations is of considerable concern in apparently drug-naive populations as it may result in treatment failure and the spread of ARV-resistant strains.

Comparison of isotope dilution with bioelectrical impedance analysis among HIV-infected and HIV-uninfected pregnant women in Tanzania.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a simple tool to assess total body water (TBW), from which body composition can be estimated using statistical equations. However, standard BIA equations have not been sufficiently validated during pregnancy, in HIV infection, or in sub-Saharan Africa. We therefore compared TBW estimates from multifrequency BIA with those from the reference method deuterium isotope dilution (Deut) in a cohort of 30 HIV-uninfected and 30 HIV-infected pregnant women from Tanzania. METHODS: We enrolled pregnant women presenting for routine antenatal care and collected data on pregnancy outcomes. At each trimester of gestation and once at 10-wk post-partum, we measured maternal anthropometry, TBWBIA, and TBWDeut. RESULTS: TBWBIA was highly correlated at each time point with TBWDeut among HIV-infected (all P ≤0.001) and HIV-uninfected women (all P <0.0001). During pregnancy, mean TBWBIA progressively underestimated TBWDeut in the overall cohort; trimester-specific differences (mean ±SD) were -1.02 ±2.36 kg, -1.47 ±2.43 kg, and -2.42 ±2.63 kg, respectively. The difference at 10-wk postpartum was small (-0.24 ±2.07 kg). In Bland-Altman and regression models, TBWBIA was subject to a systematic predictive bias at each antenatal and postnatal time point (all P ≤0.038). Among HIV-positive women, TBWDeut measured during the first (P =0.02) and second trimester (P =0.03) was positively related to birthweight. CONCLUSIONS: The validity of current BIA equations to assess TBW during pregnancy and in the postpartum period among women from sub-Saharan Africa remains uncertain. Deuterium dilution may assess aspects of maternal body composition relevant for pregnancy outcomes among HIV-infected women.

Tuberculosis in HIV-infected Tanzanian children below 14 years.

OBJECTIVE: Tuberculosis (TB)-human immunodeficiency virus (HIV) co-infection is an important public health problem. Diagnosis of TB in children usually follows discovery of an adult case, and relies on clinical presentation, sputum examination and chest radiograph. However, clinical features are non-specific, chest radiographs are difficult to interpret, and routine laboratory tests are not helpful. The aim of the current study was to determine the prevalence of TB in HIV-infected children below 14 years attending a tertiary hospital. METHODS: A cross-sectional study was conducted in HIV-infected children below 14 years of age at Muhimbili National Hospital, in Dar es Salaam, Tanzania, between July 2008 and January 2009. Information on socio-demographic and anthropometric characteristics was collected using a structured questionnaire. Following assessment of clinical presentation, physical examination, tuberculin skin test, and chest radiograph were performed for each child. Two consecutive sputum specimens and blopd sample were collected for microscopy and culture, and CD4 T-lymphocyte percentage test, respectively. Chi-square test was used to compare differences in proportions. Odds ratio (OR) and their 95% confidence interval (CI) are presented as the risk estimator. RESULTS: Of 182 HIV-infected children enrolled in the study, 104 (57.1%) were males. Overall, thirty-seven (20.3%) children had TB. The prevalence of TB was highest in males (78.4%) compared to females (p = 0.003). There was a higher proportion of TB (45.9%) in the age group below 24 months compared to other age groups (p = 0.001). Male gender, history of positive TB contact and severe immunosuppression were found to be significant risk factors for TB while use of antiretroviral therapy was found to be associated with decreased risk for TB. CONCLUSIONS: One-fifth of children had TB/HIV co-infection. Presence of four or more clinical manifestations and a low CD4+ T-lymphocyte percentage can be used to predict active TB in HIV-infected children.

Bacteria isolated from bloodstream infections at a tertiary hospital in Dar es Salaam, Tanzania--antimicrobial resistance of isolates.

OBJECTIVE: A bloodstream infection (BSI) is a life-threatening condition. We studied the causative agents of BSIs and antimicrobial susceptibility patterns of bacterial isolates at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. METHODS: A retrospective analysis of blood culture results obtained at MNH from January 2005 to December 2009 was done. Blood culture isolates judged to be clinically significant and antimicrobial susceptibility results of the bacteria were included. The frequencies and proportions of bacteria isolated and antimicrobial susceptibility results were analysed and compared using Pearson's chi-square test and Fisher's exact test where applicable, or the Mann-Whitney U-test. RESULTS: A total of 13 833 blood cultures were performed. Bacterial pathogens were detected in 1 855 (13.4%), Gram-positive bacteria (1 523; 82.1%) being significantly more prevalent than Gram-negative bacteria (332; 17.9%) (p=0.008). The most common bacterial pathogens isolated were coagulase-negative staphylococci (CoNS) (1 250; 67.4%), S. aureus (245; 13.2%), Escherichia coli (131; 7%) and Klebsiella spp. (130; 7.0%). All bacteria isolated showed high resistance to penicillin G (70.6%), tetracycline (63.8%), cefotaxime (62.5%) and ampicillin (62.3%). Moderate to high resistance was seen against chloramphenicol (45.2%), erythromycin (35.0%), ciprofloxacin (29.3%), co-trimoxazole (25.0%) and gentamicin (23.5%). Of S. aureus isolates, 23.3% were resistant to methicillin. CONCLUSIONS: CoNS accounted for two-thirds of the bacterial pathogens isolated. High-level resistance was seen to first-line and inexpensive antimicrobial agents. Routine screening for extended-spectrum beta-lactamase production and methicillin resistance among Gram-negative rods and S. aureus from blood cultures should be instituted to monitor spread of multidrug-resistant isolates.

Lipid-soluble vitamins A, D, and E in HIV-infected pregnant women in Tanzania.

BACKGROUND/OBJECTIVES: There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. SUBJECTS/METHODS: This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). CONCLUSIONS: Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions.

Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids and tocopherols in HIV-infected Tanzanian women.

BACKGROUND/OBJECTIVE: The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women. We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids and tocopherols during the first year postpartum among 626 HIV-infected Tanzanian women. SUBJECTS/METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Women were assigned to one of four daily oral supplements: vitamin A+beta-carotene (VA+BC); multivitamins (MV; B, C and E); MV+VA+BC or placebo. Concentrations of breast milk nutrients were determined by high-performance liquid chromatography at birth and every 3 months thereafter. RESULTS: Supplementation with VA+BC increased concentrations of retinol, beta-carotene and alpha-carotene at delivery by 4799, 1791 and 84 nmol l(-1), respectively, compared to no VA+BC (all P<0.0001). MV supplementation did not increase concentrations of alpha-tocopherol or delta-tocopherol at delivery but significantly decreased concentrations of breast milk gamma-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, alpha-carotene and beta-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6 and 12 months compared to no VA+BC. alpha-Tocopherol was significantly higher, while gamma-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6 and 12 months postpartum. CONCLUSIONS: Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission.

Optimal blood mononuclear cell isolation procedures for gamma interferon enzyme-linked immunospot testing of healthy Swedish and Tanzanian subjects.

Determination of antigen-specific T-cell responses is an important part of vaccine assessment. High levels of recovery, viability, and functionality of peripheral blood mononuclear cells (PBMCs) are essential for reliable assessment of cell-mediated immune responses. Here, we sought to find the cell preparation technique best suited for two clinical vaccine trial sites: Stockholm, Sweden, and Dar es Salaam, Tanzania. Standard Ficoll-Paque gradient centrifugation, BD Vacutainer cell preparation tube (CPT), and Greiner Bio-One LeucoSep tube techniques were tested. Cell yield and viability were recorded. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) testing was used to assess cell functionality. No differences in mean recovery or mean viability of fresh PBMCs were observed between Ficoll-Paque gradient centrifugation and CPT techniques as used in Stockholm. In Dar es Salaam, recovery of PBMCs isolated by use of the Ficoll-Paque gradient technique was higher than that seen with CPT (1.58 +/- 0.6 versus 1.34 +/- 0.4 million cells/ml of blood [P = 0.0469]), and the viability of PBMCs processed by Ficoll-Paque gradient was higher than that seen with CPT-purified cells (95.8% +/- 2.3% versus 92.6% +/- 4.8% [P = 0.0081]). Furthermore, LeucoSep cell separation gave higher levels of yield (1.10 +/- 0.3 versus 0.92 +/- 0.3 million cells/ml of blood [P = 0.0022]) and viability (95.7% +/- 2.0% versus 93.4% +/- 3.2% [P = 0.0012]) than Ficoll-Paque cell separation. The cells purified by the different techniques at the two sites performed equally well in IFN-gamma ELISPOT assays. Both techniques generated cell preparations with excellent yield, viability, and functionality in Stockholm. In Dar es Salaam, CPT did not perform as well as Ficoll-Paque separation. In a subsequent comparison, LeucoSep performed better than Ficoll-Paque separation. Our findings emphasize the need for on-site assessment of PBMC purification techniques for optimal evaluation of cell-mediated immune responses.

The epidemiology of HIV-1 infection in northern Tanzania: results from a community-based study.

We conducted a community-based study to determine the predictors of HIV-1 among women aged 20-44 years (N = 1,418) and their regular male partners (N = 566) from randomly selected households in Moshi, Tanzania. The weighted prevalence of HIV-1 was 10.3% in women and 7% in men. The highest risk of HIV-1 was in subjects whose partners were HIV-1 seropositive in both women (adjusted odds ratio (AOR) = 26.63; 95% confidence interval (CI): 10.74-66.02) and men (AOR = 22.25; 95%CI: 7.06-70.15). Herpes simplex virus type 2 (HSV-2) and Mycoplasma genitalium were also significantly associated with HIV-1. Women with male partners >or=12 years older than themselves had increased risk of HIV-1 (AOR = 1.99; 95%CI: 1.01-7.85). Other predictors of HIV-1 were history of infertility and the number of sex partners in the last three years in women and the age at time of circumcision and history of past sexually transmitted diseases (STDs) in male partners. These findings show that HIV-1/STDs were major public health problems among women and their long-term partners in this population. HIV-1 prevention efforts should include promotion of couple's HIV-1 counseling and testing services, control of HSV-2, promotion of safer sexual practices and strategies to reduce the age difference between women and their partners.

Levels and avidity of antibodies to tetanus toxoid in children aged 1-15 years in Dar es Salaam and Bagamoyo, Tanzania.

A study was undertaken to determine the serological response in children (aged 1-15 years) immunized with diphtheria-pertussis-tetanus vaccine (DPT) alone or with a tetanus toxoid (TT) booster dose under the Expanded Programme on Immunization in Dar es Salaam and Bagamoyo, Tanzania. Using an ELISA technique, serum levels of anti-TT antibody, antibody avidity and anti-TT IgG subclasses were determined in 138 apparently healthy children. Our findings revealed that 94.7% and 98% of children aged 1-5 years in Dar es Salaam and Bagamoyo, respectively, had anti-TT antibody levels above that considered protective (> or = 0.1 IU/ml). Among 6-15-year-old children, 53.3% in Dar es Salaam and 55% in Bagamoyo had anti-TT antibody levels > or = 0.1 IU/ml. The avidity index of anti-TT antibodies was high in most of the younger children, 84.2% in Dar es Salaam and 92% in Bagamoyo. Significantly fewer older children in Dar es Salaam and Bagamoyo (53.3% and 50%, respectively) had high avidity index antibodies. The predominant anti-TT IgG subclasses were IgG1 and IgG3. It is concluded that the current DPT immunization schedule provides adequate tetanus immunity for children under 5. However, about half of the older children had no protection against tetanus.

Antibodies to tetanus toxoid in women of childbearing age in Dar es Salaam and Bagamoyo, Tanzania.

Our aim was to determine tetanus immunity in women of childbearing age (15-44 years) with histories and/or documentation of having been vaccinated with Tetanus Toxoid (TT) under the Expanded Programme on Immunization in Dar es Salaam and Bagamoyo, Tanzania. Using an ELISA technique, serum levels of TT antibody, antibody avidity and distribution of TT IgG subclass antibodies were determined in 207 apparently healthy women. A TT antibody level of 0.1 IU/ml was considered protective. 99% and 100% of women in Dar es Salaam and Bagamoyo, respectively, had a TT antibody level > or = 0.1 IU/ml. Anti-toxin binding avidity was found to be high in most of the women. In addition to TT IgG3 subclass antibody, TT IgG1 subclass antibody was the most dominant subclass type. A substantial number of women also had TT IgG2 and TT IgG4 subclass antibody responses. A better recording system on TT immunization is recommended to avoid hyper-immunization of women and to optimize the cost-effectiveness of the immunization programme.